Genetics Flashcards
DNA in proks vs euks
single chrm that’s supercoiled and attached to RNA-protein core, in nucleoid/cyto, can also have plasmids vs mult chrms in nucleus/mito/chloroplasts, DNA binds to histones => chromatin
Gene expression requires what 2 processes?
transcpxn/RNA synthesis and transln/protein synthesis; regulation of gene expression determines which proteins are synthesized
Nucleosides vs nucleotides
pentose + nitrogenous base at C1 vs pentose + nitrogenous base at C1 + phosphate(s) at C5 (alpha/beta/gamma phosphates)
Ribose vs deoxyribose
Has -OH at C2 vs has -H at C2
Leon Heppel vs Watson and Crick
proved that inorganic phosphate joined w/ nucleotide monomers in early 1950s; nucleotide monomers join by alpha phosphate via phosphodiester bond –> beta and gamma phosphates = cleaved off vs DNA = antiparallel double helix w/ 2 polynucleotide strands joined by base pairing
describe double helix
B FORM (right handed helix); stabilized by H bonds, vdw interactions, hydrophobic effect; major grove/big gap, minor groove/little gap; net neg charge b/c 3rd -OH group of phosphate = free
what can heat vs alkali do to DNA?
both denatures double helix. converts dsDNA to ssDNA => melting; if temp dec –> reannealing/renaturation/hybridization vs double helix separates but not break phosphodiester bonds (it does in RNA)
doxorubicin vs azithromycin vs ciprofloxacin vs melanomas
intercalates b/w base pairs –> inhibits replication and transcpxn; stops/slows growth of ca cells vs inhibits protein synthesis on prok 50S ribosomal subunit (euks don’t have 50S) vs inhibits bacterial DNA gyrase –> inhibits bacterial DNA synthesis (euks have linear DNA and don’t have DNA gyrase) vs UV causes pyrimidine dimers –> mutation from nonrepair of dimers
describe chromatin
DNA + nucleosome = chromatin; 2 molec of H2A/H2B/H3/H4 make up core, H1 binds to linker DNA b/w nucleosome beads; when strings of nucleosomes wind into helical and tubular coils => solenoid structure/polynucleosome/30nm-fiber
know diff b/w D/RNA
look at the table in Lecture 1
mRNA vs rRNA vs tRNA
contains nucleotide seq that’s converted to aa seq of protein; in proks: generated from operon as polycistronic transcript and transcribed; in euks: pre-mRNA processed in nucleus to mature monocistronic mRNA and then leaves nucleus to cytosol vs subcellular ribonucleoprotein complexes where protein synthesis occurs vs carry aa to ribosomes; cloverleaf (3 loops), 2nd loop has anticodon, 3’ end has aa attachment site
what # is mito ribosome?
55S (similar to 70S in bacteria)
what are the exceptions to central dogma?
viruses have either D/RNA and need hosts to replicate; genetic material = protected by protein coat, protein coat protected by lipid envelope. RETROVIRUSES - have reverse transcriptase to go from RNA to DNA
know diff b/w proks/euks
there’s a summary table in Lecture 1
origin of replication (ori)
includes short AT-rich segments where DNA synthesis occurs; proks have one ori, euks have mult ori; dsDNA unwinds and separates –> 2 rep forks in opposite directions => bidirectional
major players of DNA separation for replication
DNA helicase; single stranded DNA binding proteins - prevent strands from reassociating and protect strands from enzymatic cleavage (ex: RPA); DNA topoisomerase - removes pos and neg supercoils (ex: DNA gyrase)
describe the enzymes involved in DNA synthesis
primase makes RNA primer and pol α adds a couple bases and leaves (they also start Okazaki fragments) –> pol ε adds nucleotides on leading strand, pol δ adds nucleotides on lagging strand (stops adding when reaching start of next frag); both proofread (3’-5’ exonuclease activity then 5’-3’ endonuclease activity) –> flap endonuclease 1 (FEN1) and RNAse H remove RNA primers via 5’-3’ exonuclease activity –> pol δ fills in gap from RNA primer –> DNA ligase glues frags together
primase for proks vs euks
DnaG vs pol α
telomeres vs telomerase vs telomere shortening
complex of noncoding NA + protien at end of linear euk chrm –> maintain structural integrity of chrm; tandem rpts of noncoding hexameric seq: TTAGGG vs maintain telomeric length in germ/stem/ca cells; acts as reverse transcriptase; short RNA seq template => Terc; resolves senescence; look at pic in Lecture 2 vs can lead to senescence which can be good b/c reduce mutation risk
what happens if cells can’t repair dmged DNA?
- senescence or irreversible dormancy
- apop
- malignant uncontrolled cell division
somatic mutations vs germline/genetic mutations
in cells not involved in gamete prod, no change in phenotype, basis of most ca vs in cells involving gametes –> hereditary
sources of DNA dmg
exogenous/environ: ionizing rad like UV and xrays, chemicals like DNA alkylating agents and procarcinogens vs endogenous: hydrolysis rxns (depurination, depyrimidation), [O] of bases –> ROS, mutations in S phase
3 major mechanisms for ssDNA repair: nucleotide excision repair vs base excision repair vs mismatch repair
LOCAL distortions of DNA helix –> nuclear endonucleases recognize and cleave abnl chain on 3’ & 5’ side of distorted region –> short oligonucleotide w/ distortion = released –> gap in DNA –> DNA pol and ligase fill in gap (ex: repair pyrimidine dimers) vs DNA lesions involving base alterations or spontaneous loss –> specific glycosylases cleave base –> apurinic/pyrimidinic site (AP site) –> AP endonucleases recognize missing base and make endonucleolytic cut on 5’ side –> deoxyribose phosphate lyase removes the sugar/phosphate hanging out –> DNA pol and ligase complete repair vs non-dmged mismatched bases after DNA pol proofreading error/slip –> in proks: find degree of methylation, in euks: find nicks in strands and how Mut proteins interact w/ PCNA –> endonuclease cuts into strand –> exonuclease removes mismatched bases –> DNA pol and ligase complete repair
xeroderma pigmentosum (XP) vs cockayne syndrome & trichothiodystrophy
d/o of NER –> ability to fix DNA dmg from UV = deficient –> freckles & most likely skin ca; children of the night vs d/o in NER and transcpxn-coupled repair from mutations in ERCC6 or ERCC8 genes caused by UV, chemicals, free rad –> NO skin ca, fail to thrive, premature aging
microsatellite instability (MSI)
caused by mutations in MMR genes; if inherited –> predisposed to hereditary nonpolyposis colorectal ca (HNPCC); test for MSI = diagnostic for colon ca. microsatellite = short tandem rpts that can tell you if mutations are occurring elsewhere
double stranded break repair vs homologous recombination vs non-homologous end joining
hazardous forms of DNA dmg leading to genome rearrangement, mutations and cell death; 2 repair mechanisms: HR and NHEJ but defects in these repair mechanisms –> genetic dz vs only used when homologous DNA = present; BRCA1 and BRCA2 w/ RAD51 maintain strand invasion –> homologous DNA frag restore dmged DNA –> error free vs don’t need homologous template –> protein KU recognizes and binds exposed ends => directly join broken ends –> imprecise repair b/c you lose the nucleotides from orig DNA strand
Ataxia Telangiectasia (AT) vs Burkitt’s Lymphoma
defect in ATM kinase –> doesn’t activate checkpoints in response to DNA dmg (usually they help cells recognize dmged or broken DNA strands and coordinate repair) –> inc risk of leukemias and lymphomas. sxs: telangiectasia (broken blood vessels), ataxia (progressive neuro impairment and difficulty coordinating movement) vs caused by c-myc gene classic t reciprocal translocation and deregulation on chrm 8; c-myc = transcriptional activator (proto-oncogene) that affects diff pathways for regulating cell cycle, growth, adhesion, differentiation, and apop; overexpression —> deregulation of cell cycle control
missense vs frameshift mutation
single base = diff –> diff aa vs insertion/deletion of single base changes reading frame
diff mods after transcribing pre-mRNA
splicing, reading frame, polyadenylation, RNA editing (ex: RNA editing of glutamate receptor by changing adenosine to inosine), RNA export, RNA localization
centromere. meta vs submeta vs acrocentric centromere
separates chrms into P and Q arm; based on P arm size compared to Q arm. mid vs a little higher than mid vs very high –> smallest P arm
idiogram vs karyotype
drawing of chrms vs photograph of chrms from light microscopy arranged in order; stains during metaphase; use to analyze 5mil bp
which chrms are acrocentric?
13-15, 21-22 = AUTOSOMAL ACROCENTRIC
G banding. advantages vs disadvantages
geimsa stain; stains AT rich –> less and darker, GC rich –> more and lighter. see large abnlities, easy to perform, reliable vs can’t see small abnlities
why use karyotype? when?
problems w/ early growth/development, fertility problems, neoplasia, high risk pregnancy. >5mil bp
X activation/Lyonization
random epigenetic inactivation of 1 copy of X chrm in females –> Barr body formation; depends on XIST found in X inactivation center (XIC) (no XIC –> no inactivation –> show both X chrms)
SRY gene vs pseudoautosomal regions
present on Y chrm; testis-determining factor; males = hemizygous b/c only have 1 Y gene; if SRY gene on XX –> female w/ testis, if SRY gene not on XY –> male w/ no testes vs PAR1 and PAR2: homologous seq found on sex chrms
prophase and prometaphase. know MAT as well
nuclear envelope break down, microtubules attach to centromere, chrms start to condense
prophase I vs metaphase I vs anaphase I vs telophase I
chrm coil and form a bridge –> synapsis of homologs => synaptonemal complex –> crossing over –> inc genetic variation vs random alignment of bivalents –> indep assortment –> inc genetic variation vs homologous chrms move to opposite sides but sister chromatids still attached at centromere vs cell division, chrms uncoil, nuclear membrane reforms –> cytokinesis but NO DNA replication for meiosis II
chromosomal abnlities: numerical vs structural
euploid = exact correct #, aneuploid = abnl # like trisomy or monosomy, polyploidy = have more than 2 complete sets of chrms (>2n) like triploidy (caused by fertilization of 1 egg + 2 sperm => dispermy, or failure of meiosis –> diploid egg/sperm –> miscarriage)
meiotic nondisjunction I vs II
gametes have 2 whole chrms 21 or none vs gametes have 2 copies of chrm 21 or none. check Lecture 9 Slide 10
numerical: mosaicism vs chimera
1 zygote to 2+ pop of cells in 1 individual; caused by mitotic error/mutation in embryo development (gain/lose chrm by nondisjunction); somatic: symptomatic but not inheritable, germinal: asymptomatic but heritable vs 2 zygotes in 1 individual (dizygotic fraternal twins –> 1 twin absorbs dead twin)
numerical: autosomal aneuploidy: trisomy 21 vs 18 vs 13
palmar crease, intellectual disability, congenital heart dz and leukemia vs 1/6000, rarely live past 1st year, clenched fist w/ 2nd and 5th digits overlapping 3 & 4 vs 1/8000, die w/in first days/weeks, polydactyly, cleft palette, cutis aplasia (missing parts of scalp)
numerical: sex chrm aneuploidy: XXY vs XO vs XXX vs XYY
tall, hypogonad b/c low testosterone –> infertile, but fairly nml vs short, amenorrhea –> infertile, webbed neck vs tall, increased risk of learning disabilities, but phenotypically nml vs associated w/ acne and learning disabilities, but phenotypically nml
structural abnllities can be balanced vs unbalanced
don’t lose genetic info –> asx but inheritable vs lose genetic info –> symptomatic (ex: deletion, duplication)
structural: deletion vs duplication vs isochrome vs translocation vs inversion
gene = inactivated/deleted and remaining fxnal copy of gene = not adeq to preserve nml fxn –> haploinsufficiency; can result in monosomy depending on size (ex: William’s syndrome = del of 7q11.23, elastin/ELN gene in this region –> affects elastic fibers and connective tissue: DiGeorge’s syndrome) vs can result in trisomy depending on size (ex: cat-eye syndrome: cardiac defects, cleft palate, skel and kidney problems, hernias, intellectual disability) vs chrm where 1 arm = lost –> other arm = duplicated in mirror fashion; 3 copies of 1 arm = partial trisomy, 1 copy of 1 arm = partial monosomy vs when chrm breaks into frag and frags reattach and diff locations –> still balanced; Robertsonian - joining long arms of acrocentric chrms –> balanced b/c p arms only have rRNA, Reciprocal - exchanging 2 chrm segs b/w 2 chrms –> even and balanced vs 2 breaks in 1 chrm that could be in one arm/doesn’t include centromere => paracentric or 1 in each arm/include centromere => pericentric
aminoacyl-tRNA synthetase
attaches correct aa to correct tRNA, requires ATP; enzyme has proofreading ability
genetic code
specific, universal (specificity = conserved since early stages of evolution), degenerate/redundant (1 aa can have mult codons)
IRES. how are viruses involved?
initial ribosome entry site - shunts ribosome to second AUG and begin second transln. when cells = stressed –> transln shuts down –> virus use their IRES to start viral transln while host transln = down
cap dep vs indep activation
when cells = stressed (hypoxia, infxn, apop, oncogenes): dec vs inc; uses IRES
sickle cell anemia
periodic episodes of pain => crises; sickled-shape RBC block blood flow, break apart easily and die –> anemia, can’t carry enough O2 –> fatigue, dmgs spleen; protective against malaria => heterozygote advantage
gain of fxn vs loss of fxn vs dominant neg mutation
mutation resulting in new, increased, or unregulated activity for protein; can be frameshift; can be deleterious vs mutation resulting in lost activity for protein; can be frameshift; can be deleterious vs mutation resulting in lost activity and shuts down activity of unmutated proteins
DNA polymerase vs heat stable DNA polymerase vs DNA ligase vs RNA polymerase vs Reverse Transcriptase
adds bases from 5’ to 3’ direction vs a class of DNA polymerases isolate from thermophilic bacteria –> remains active at high temps; Taq DNA polymerase = most common for PCR and cycle sequencing vs forms phosphodiester bond b/w 2 DNA strands; used in cloning vs makes RNA molec complementary to DNA template vs makes DNA molec complementary to RNA template; used for cDNA prod and identifying transcriptional start sites of genes
What are restriction enzymes/restriction endonucleases?
Enzymes that recognize SPECIFIC dsDNA 4-8bp seq, particularly palindromic —> once they find the seq, they cleave the phosphodiester bond of DNA backbone; they yield sticky or blunt ends. Used in cloning and some diagnostic assays
techniques for amplifying DNA: cloning vs DNA libraries vs PCR
take DNA you want amplified (foreign DNA) and attach it to vector (carrier DNA) –> introduce foreign DNA+carrier DNA to host cell –> host cell replicates its own DNA and foreign+carrier DNA; vectors can be bacteria host (transformed cells) like plasmids/bacteriophage/cosmids or euk host (transfection or transduction) like free DNA/DNA coated w/ lipid layer (liposome)/retro or adenoviruses (transduction-virus)
Genomic libraries vs cDNA libraries
Large DNA fragments contains both coding and noncoding genes —> can’t be used for recombination vs small DNA fragments containing coding genes aka exons —> can be used for recombination; made from reverse-transcribing mRNAs
Know ab and ag for ABO
Memorize the table in Lecture 10, Slide 4
Mendelian d/o and types
genetic d/o caused by single genetic locus. autosomal dom/rec, X-linked dom/rec, Y-linked, mitochondrial
Know pedigrees. How to know if auto rec vs auto dom vs x linked rec vs x linked dom
Lecture 10, Slide 7. both M/F, rare vs both M/F, common, father/son, only 1 dominant allele to show trait vs only males, no father/son vs both M/F but more F, no father/son, fathers can pass to daughters
autosomal recessive d/o vs consanguinity vs autosomal dom vs assortative mating
you inherit 2 mutated genes (1 from each parent) vs conseq of consanguineous mating that inc chance of recessive dz w/in fam vs you inherit 1 mutated allele vs form of sexual selection where individuals w/ similar phenotypes mate w/ another at a higher rate than expected (even tho it was random)
penetrance vs variable expressivity vs locus heterogeneity vs allelic heterogeneity
probability that ppl w/ a mutant allele will actually express that associated trait/dz; ex: Treacher-Collins syndrome, split-hand deformity vs degree of expression of a phenotype from same genotype; CF, Emery-Dreifuss muscular dystrophy vs mutations at mult genes from single or mult chrms can produce same phenotype and each mutation = sufficient to cause dz independently vs different alleles/variants of single gene can cause same/similar dz
examples of auto rec vs dom dz
Tay-Sachs dz (defic in HexA enzyme), PKU (defic in phe hydroxylase enzyme –> can’t metab phe into tyr), sickle cell, CF, cartilage- hair hypoplasia dwarfism vs achondroplasia, Marfan syndrome (connective tissue d/o), brachydactyly, Huntington’s dz
examples of x-linked recessive vs dominant d/o
Duchemme muscular trophy: thigh atrophy/bigger calves, paralysis, infertile, death; hemophilia dz affecting Factor IX vs hypophosphatemia, Incontentia pigmenti (F w/ x linked dom w/ mosaic pattern b/c nml X chrm = inactivated; lethal in males)
common sxs of mito dz
poor growth, muscle weakness, vision problems, heart/liver/kidney dz, neuro problems; no cures for mito dz
homoplasmy vs heteroplasmy
all copies of mtDNA in a euk cell = identical vs copies of mtDNA in a euk cell = diff from e/o
myoclonic epilepsy w/ ragged red fibers (MERRF)
mito tRNA mutated –> myoclonus, epilepsy, ataxia, dementia
leigh syndrome
severe neuro d/o by progressive loss of mental and movement problems; involved in nuclear AND mito DNA; sxs: N/V, difficulty swallowing/dysphagia, fail to thrive; death by 2-3 yo
Chromosome Territory vs Transcpxn Factory
hypothetical compartment where most of a chromosome resides in a highly condensed state and no genes are expressed vs protein machinery required for DNA transcpxn; when you need to transcribe a gene –> loop gene out of chm territory to transcpxn factory
CTCF (CCCTC-binding factor) vs cohesin
CTCF binds to certain site along the chromosome and serves as a blocking point and anchors loops vs DNA loops through cohesin circles. CTCF interacts with cohesin to stop the extrusion of DNA and control the size of the chromosomal loops
Levels of gene expression regulation
1: directing DNA loops out of chrm territory and to transcpxn factory
2: nucleosome/nucleosome code mod - TF binds to promoter –> histone tails = modified around gene of interest –> some nucleosomes = removed or repositioned to allow more access to DNA helix for other proteins involved in the regulation of gene expression
Steps of transcpxn
1) initiation: TFs bind to cis elements and interact w/ pre-initiation complex; TATA binding protein bind to TATA box within promoter region –> guides RNA Polymerase II to TATA in promoter; regulate by proximal/distal promoter elements
2) elongation: unwinds DNA via helicase, relieve torsional stress via topoisomerase, and make pre-mRNA aka heterogenous nuclear RNA (hnRNA) via RNA polymerase; CTD influences elongation. Transcpxn doesn’t require primers
3) termination: release factor disrupts RNA/ribosome complex
4) CTD recruits spliceosome composed of snRNA and snRNPs to splice introns out (though sometimes pre-mRNA doesn’t always have introns)
5) mRNA = cleaved –> 5’ guanine cap added and 3’ poly A tail added to maximize stability when mRNA leaves nucleus to cytosol for transln
6) RNA editing - creates specific protein sequences from an RNA that didn’t encode a functional protein
3 diff RNA pol = involved w/ transcpxn and each have diff transcpxn complexes
Pre-Initiation Complexes that must be assembled right on core promoter before transcription can begin; after last subunit comes in => transpxn complex
upstream control elements: proximal control elements vs distal control elements
TATA box = not universal. CAAT box and GC box found in very strong promoter further upstream from core promoter; operate just on one gene vs operate in both directions –> affects more than one gene
Pol I and Pol III promoters do not have many upstream control elements as they control the transcription of genes that are expressed in all cells at all times. Pol II promoters have more regulation as the genes they direct as expressed in very controlled situations
promoter proximal elements/elements of the Core Promoter vs promoter distal elements
upstream DNA seq influencing promoter activity vs includes enhancers, silencers, or insulators (cis elements that stimulate transcription vs cis elements that shut down transcription vs create a boundary between one gene and the next to prevent the histone code from one region to stray into a neighboring region and influence the expression of neighboring genes)
cis elements vs trans-acting/transcpxn factors
DNA sequences that define where transcription factors can bind; can by unavail if not in transcpxn factory or if they’re held tightly –> can’t bind to transcpxn factors vs protein components that bind to these elements; can stimulate or repress the initiation of transcription by interacting w/ pre-initiation complex
focused/sharp type vs dispersed/broad type promoters
start at same place same time vs start in general vicinity. both = based on how the pre-initiation complex is assembled to position RNA pol and what promoter elements were used
CTD
w/in largest subunit of RNA pol; can by phosphorylated or glycosylated –> D determines what protein partners bind to the advancing polymerase and influence activities.
synonymous mutation vs non-synonymous mutation
does not change the amino acid sequence (silent mutation) vs does change the amino acid sequence (nonsense, missense, frameshift)
fxns of 5’ guanine cap vs polyA tail
protects the RNA from degradation by exonuclease vs protects mRNA from 3’ exonuclease digestion, interacts with the cap to circularize the mRNA, facilitates interaction with the ribosome
guide RNAs
guides modification of ribosomal RNAs, polymerization of telomeres, and cleavage and polyadenylation of mRNAs
spinal muscular atrophy vs hutchinson-gilford progeria syndrome vs myotonic dystrophy
mutation in SMN1 gene (SMN = used for snRNP synthesis) –> SMN2 gene destroys splicing enhancer and creates splicing silencer –> deficient SMN protein –> degeneration of motor neurons vs muttaion in lamin A/C gene –> incorrect splicing –> truncated protein –> can’t be post-modified –> premature aging vs expansions in genes have high affinity to splicing factor MBNL1, but if you deplete MBNL1 –> disrupt alt splicing –> myopathy/tonia, cardiac defects
where are ribosomes found?
almost everywhere in cell even in nucleus
untranslated region (UTR)
contains sequences that assist in binding to the ribosome and regulate translation
charged tRNA
amino acid covalently attached to the 3’ end of the tRNA via Aminoacyl-tRNA synthetase (requires ATP) –> is primed for translation. two step process: amino acid is first attached to an AMP molecule, and then transferred to one of the tRNAs for that amino acid => second genetic code
Describe EPA sites
Aminoacyl - tRNA + aa (charged tRNA) comes in
Peptidyl - where peptide builds up via peptide bonds
Exit - where free tRNA leaves
Steps of transln
1) initiating tRNA+met binds to small 40S ribosomal unit —> 40S binds to 5’ cap –> 40S scans along mRNA till it reaches start codon –> large 60S ribosomal unit binds to mRNA; OR ribosome binds to internal ribosome entry site (IRES) of mRNA and start transln w/o looking for start codon (used for translating 2nd open reading frame)
2) ribosome moves in 5’ to 3’ direction and starts adding bases from start codon
3) translation continues till it reaches stop codon. tRNA doesn’t have an anticodon when reaching stop codon –> release factor protein aka eukaryotic translation termination factor 1 (ETF1) binds to stop codon and disrupts ribosome/mRNA complex and releases polypeptide
selenocysteine aa
found in active site of detoxifying enzymes; Selenocysteine tRNA is initially charged with serine, which is modified and then replaced with selenocysteine. RNA seq encoding selenocysteine has hairpin structure –> selenocysteine cis element (SECIS) interacts with ribosome to facilitate binding of selenocysteine tRNA.
proper protein folding = dependent on?
partially dependent on the amino acid sequence (encoded in the genome) and partially upon a network of helper molecules that prevent the accumulation of poorly folded and thus nonfunctional proteins
tert folding = determined by?
hydrophobic interactions, ionic interaction with cations, some electrostatic interactions between charged amino acids like H bonds, and disulfide bonds
chaperones
help correctly fold newly synthesized proteins via ATP => foldase; bind to folding intermediates to prevent aggregation => holdase; shuttle polypeptides to a place where they complete assembly => “escort”,
bind misfolded proteins and escort them to proteasome for degradation; and target aggregates to larger digestive organelles
aa seq determines where protein will end up in cell. describe 1st post translational mod
signaling recognition particle (SRP) binds to signal seq/peptide –> escorted to SRP receptor in ER –> docked and transln cont –> polypeptide = injected into ER lumen –> when done translating, signal seq cleaves off
fates of proteins translated in ER lumen or its membrane
can mature in ER or golgi
fxns of proteolysis
activate a protein, deactivate a protein once it completed its job, portion of the translated polypeptide = removed to create the final protein, a protein has one job until an enzymatic cleavage cuts the protein releasing a frag that has a completely different role in the cell
fxns of phosphorylation
activation or inactivation of a protein; major sites = ser, thr, tyr (but other aa can be phosphorylated)
fxns of glycosylation
found on secreted proteins and membrane bound proteins; regulation of cell-to-cell binding; target proteins to specific sites in the cell, like the lysosome (branched sugar = attached to polypeptide and cont transln –> moves to Golgi –> N-acetylglucosamine phosphate is added to the terminal mannose residues –> N-acetylglucosamine = removed to leave phosphorylated terminal mannose residues –> protein binds to receptors w/ mannose 6 phosphate marker –> goes to transport vesicle –> fuse w/ endosome and drop cargo –> endosome becomes lysosome containing hydrolytic enzymes; In the absence of mannose phosphorylation, the enzyme is secreted into the extracellular space instead of lysosome (lack of lysosomes –> structural defects in cells)
p53 post-translational modification:
deregulated in tumorigenesis
fxns of lipidation
target proteins to membranes in organelles (endoplasmic reticulum [ER], Golgi apparatus, mitochondria), vesicles (endosomes, lysosomes) and the plasma membrane by inc hydrophobicity –> inc affinity to membranes; 4 types: C-terminal glycosyl phosphatidylinositol (GPI) anchor, N-terminal myristoylation, S-myristoylation, S-prenylation
Mito fxn depends on?
Nuclear and mito DNA
Human Genome Project goals
determine seq of 3.2b bases that make up human DNA, identify all genes in human DNA, compile comprehensive polymorphism databases, develop tools for data analysis, fostering biotech innovation, address legal/ethical/social issues that arise from genome research
Human Genome Project reference genome
composite genome from several diff ppl; generated from 10-20 primary samples from anon donors across racial and ethnic groups
largest gene vs largest protein
dystrophin/DMD gene at 2.4Mb; mutations cause muscular dystrophy vs titin/TTN b/c most exons
pseudogenes
genes lost d/t mutations in evolution –> can tell us how we evolved
ncRNA vs siRNA
transcribed into RNA but not translated into protein vs involved in gene regulation by binding to mRNA
2 classes of transposable/mobile elements
retrotransposons/Class I that break into LTR retrotransposons like retroviruses or non-LTR retrotransposons like LINES/SINES vs DNA transposons/Class II
retrotransposons/Class I vs DNA transposons/Class II
copy and paste mechanism –> mutagenic; use reverse transcriptase vs cut/paste mechanism; use transposase
LTR retrotransposons vs non-LTR retrotransposons
endogenous retroviruses, retroviral genomes integrated in vertebrates, decayed relic of viruses vs LINEs (long interspersed nuclear elements), contain RT, probs involved in transposition, LINE-1 = most abundant human LINE (516k copies), 6.1kb long; SINEs (short interspersed nuclear elements), don’t have RT but can borrow it from retroelements, Alu = most abundant human SINE (>1mil copies), 300bp long
minisatellite vs microsatellite
10-100s bps, can be VNTR, can be used in forensics vs <10 bps, like telomere seq TTAGGG. both can expand or contract (contract in humans), both prone to mutations b/c DNA pol slips off –> loops –> returns to work
anticipation
dz inc in age of onset in successive generations –> children have more severe form than parents
Huntington’s dz
nml rpt = 9-29; adult mutation = >40, juvenile mutation >60; sxs: mood change, motor abnormalities mid-life (30/40s) –> involuntary twitching, loss of cognition –> death
